Human immunodeficiency virus type 1 infection of human placenta: potential route for fetal infection.

To determine the potential role of the placenta in transmission of human immunodeficiency virus (HIV) from mother to fetus, the ability of human placental tissue to support HIV type 1 (HIV-1) infection was examined. HIV-1-seronegative first-trimester placentas were maintained in culture and infected with HIV-1. Virus production, measured by HIV-1 antigen release into the supernatant, and HIV-1 DNA, identified by polymerase chain reaction, were detected for at least 12 days postinfection. Western immunoblot analysis showed Gag proteins, precursor p55, and cleavage products p24 and p17 in HIV-1-infected tissues. Double labeling of placental villi with antibodies to CD4 and placental trophoblast-specific alkaline phosphatase indicated that trophoblasts express CD4 antigen. Additionally, immunostaining of HIV-1-infected tissues with anti-p24 antibodies demonstrated HIV-1 protein expression in placental trophoblasts. Evaluation of human chorionic gonadotropin and progesterone production by the placental cultures indicated that there was a 90% decrease in human chorionic gonadotropin and a 70% decrease in progesterone production in HIV-1-infected cultures in comparison with controls. These data demonstrate that trophoblastic cells of human placenta tissue express CD4 and are susceptible to HIV-1 infection; also, placental endocrine function is decreased by HIV-1 infection. Thus, the placenta may serve as a reservoir of HIV-1 infection during pregnancy contributing to infection of the fetus, and decreased placental hormone production may result in impaired fetal development.

Persistence of human cytomegalovirus DNA sequences without cell-virus homology in human placental explants in culture.

Using histopathology, virology, and molecular probing, we investigated the potential of human first-trimester placental tissue to support human cytomegalovirus (HCMV) infection. Histopathologic examination of infected placental explants revealed cellular changes characteristic of HCMV infection. Immunohistochemical staining of infected explants with human convalescent sera demonstrated expression of HCMV antigens within the cytotrophoblast. Dot blot hybridization of DNA extracted from infected placental tissue using cloned Hind III "W" fragment of HCMV genome indicated the presence of HCMV sequences without virus-cell homology in infected explants from one to ten days post-infection. In general, the sequences detected by the viral probes increased in abundance with time as infection continued.

Human cytomegalovirus infection of human placental explants in culture: histologic and immunohistochemical studies.

The induction of human cytomegalovirus infection in human first-trimester placentas was studied with a placental explant culture model. Replication and/or release of human cytomegalovirus in placental explant cultures did not occur at any time from 1 to 10 days after infection when examined by plaque assay and analyses of extracted deoxyribonucleic acids. In contrast, typical human cytomegalovirus-induced histopathologic lesions bearing human cytomegalovirus antigens were consistently localized in the trophoblastic cells covering placental villi. These data clearly demonstrate that placental cells are permissive of latent and/or abortive human cytomegalovirus infection in vitro. Our results support the hypothesis that during human cytomegalovirus infection of pregnant women, maternal viremia or intrauterine infection results in latent human cytomegalovirus infection of placental cells that may persist during the course of pregnancy.